Journal Mobile Options
Table of Contents
Vol. 225, No. 1, 2012
Issue release date: October 2012
Section title: Original Paper
Dermatology 2012;225:88–92
(DOI:10.1159/000341534)

Reduced Number of Circulating Endothelial Progenitor Cells (CD133+/KDR+) in Patients with Plaque Psoriasis

Batycka-Baran A.a · Paprocka M.b · Krawczenko A.b · Kantor A.b · Duś D.b · Szepietowski J.C.a
aDepartment of Dermatology, Venereology and Allergology Wroclaw Medical University, and bInstitute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
email Corresponding Author

Abstract

Background: Psoriasis is associated with an increased cardiovascular risk. Circulating endothelial progenitor cells (CEPCs) play a significant role in the maintenance of vascular homeostasis. Objective: The aim of this study was to evaluate the number of CEPCs in patients with psoriasis compared to controls and assess possible correlations between the number of these cells and the plasma levels of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and clinical features of psoriasis. Methods: The number of CEPCs, identified as CD133+/KDR+ cells, was determined with flow cytometry in peripheral blood of psoriatic patients (n = 63) and controls (n = 31). The plasma levels of VEGF and sVEGFR-1 were measured with enzyme-linked immunosorbent assay. Results: The number of CEPCs was significantly reduced in psoriatic patients compared with controls (p = 0.000026) and inversely correlated with disease severity (R = –0.283; p = 0.0248). Conclusion: A reduced number of CEPCs may contribute to endothelial dysfunction in patients with psoriasis.

© 2012 S. Karger AG, Basel


  

Key Words

  • Circulating endothelial progenitor cells
  • Psoriasis
  • Endothelial dysfunction
  • Atherosclerosis
  • Cardiovascular risk

 Introduction

Psoriasis is a chronic, immune-mediated inflammatory disease (IMID) of the skin. Numerous studies have demonstrated an increased cardiovascular risk in patients with psoriasis. Growing evidence indicates an important role of endothelial dysfunction and chronic inflammatory process in the pathogenesis of atherosclerosis [1,2,3,4,5]. Circulating endothelial progenitor cells (CEPCs) constitute a minor population of bone-marrow-derived cells in peripheral blood that possesses the capacity to migrate, proliferate and differentiate into mature endothelial cells. Numerous studies indicated their significant role in the repair of endothelial injury and formation of new blood vessels, in a process termed postnatal vasculogenesis. Depletion of CEPCs has been postulated to have significant relevance to the pathogenesis of atherosclerosis [6,7,8,9]. In the current study we attempted to evaluate the number of CEPCs, identified as CD133+/KDR+ cells in peripheral blood, in patients with plaque psoriasis compared to the control group. We also assessed the possible correlations between the number of these cells and the plasma levels of vascular endothelial growth factor (VEGF), soluble receptor 1 for this factor (soluble vascular endothelial growth factor receptor-1, sVEGFR-1) and clinical features of psoriasis.

 Subjects and Methods


 Subjects

63 patients with plaque-type psoriasis were recruited to the study. 31 subjects with no history of skin disease, matched by age and gender, served as controls. Exclusion criteria included: known cardiovascular disease, chronic renal or liver disease, diabetes mellitus, skin disease, malignancies or any significant abnormalities in blood count. The psoriatic patients had not received any topical or systemic therapy for at least 3 months prior to the initiation of the study. Demographic data as well as information regarding the presence of traditional cardiovascular risk factors, medication use, onset and duration of psoriasis were documented (table 1). The severity of disease was assessed with the Psoriasis Area and Severity Index (PASI). There were no statistically significant differences (p > 0.05) regarding the incidence of assessed cardiovascular risk factors and medication use between psoriatic patients and controls. The study was approved by the local Bioethical Committee according to the Helsinki Declaration (No. 283/2008).

TAB01
Table 1. Clinical and demographic characteristic of the study group

 Methods

The evaluation of CEPC numbers was performed with flow cytometry, using a FACSCalibur cytometer (Becton Dickinson). Peripheral blood samples were incubated with FcR-blocking reagent (human FcR Blocking Reagent, Miltenyi Biotec GmbH) and then with selected antibodies (anti-human CD133 APC, eBiosciences; anti-human VEGFR-2 (KDR)-phycoerythrin-conjugated mouse IgG1, R&D Systems) at the concentrations suggested by the manufacturer. Isotype-matched, labeled immunoglobulins (Mouse γ1 APC, BD Biosciences; Mouse IgG1 Isotype Control Phycoerythrin Conjugated, R&D Systems) were used for each samples as negative control. After incubation, cells were treated with lysing solution (Lysing Solution, BD Biosciences) to eliminate erythrocytes. Fluorescent CytoCount beads (Dako Cytomation) were added for the evaluation of the precise cell number. A minimal number of 150,000 events were collected. CEPCs were evaluated using the gate for lymphocytes and data were expressed as cell count per 1 ml of blood.

The levels of VEGF and sVEGFR-1 were measured with enzyme-linked immunosorbent assay, using commercially available kits (Quantikine Human VEGF Immunoassay, R&D Systems and Quantikine Human sVEGFR-1/Flt-1 Immunoassay, R&D Systems, respectively), according to instructions of the manufacturer.

The statistical analysis was performed using the software Statistica version 9.0 (system Windows XP). The mean, median, maximal, minimal and standard deviation of values was calculated. The U-Mann-Whitney test was used to compare continuous variables. The significance of differences between categorical variables was determined by χ2 Pearson test, χ2 with Yates correction test or Fisher’s exact test. The relations between continuous variables of interest were assessed by Spearman’s rank correlation coefficient. Statistical significance was set at p < 0.05.

 Results

The number of CEPCs was significantly reduced in psoriatic patients compared with the control group (p = 0.000026) (table 2). The level of CEPCs was inversely correlated with disease severity assessed with PASI (R = –0.283; p = 0.0248) (fig. 1). There were no significant correlations of CEPCs number with the gender of patients, onset and duration of psoriasis, duration of present exacerbation of disease, smoking habit, obesity or hypercholesterolemia (data not shown). The number of CECPs was significantly reduced in psoriatic patients with arterial hypertension (251.4 ± 150.06 ml) compared to those with normal blood pressure (397.97 ± 190.36 ml) (p = 0.0187). The plasma level of VEGF was significantly increased in psoriatic patients compared with controls (p = 0.00032) (table 3). There was no significant difference in the level of sVEGFR-1 between psoriatic patients and controls (p = 0.748) (table 3). No significant correlations between the number of CEPCs and the levels of both VEGF (p = 0.214) and sVEGFR-1 (p = 0.187) were found.

TAB02
Table 2. Reduced number of CEPCs per milliliter in patients with plaque psoriasis and controls

TAB03
Table 3. Plasma levels of VEGF and sVEGFR-1 in patients with plaque psoriasis and controls (mean 8 SD)

FIG01
Fig. 1. Inverse correlation between the number of CEPCs and disease severity assessed with PASI.

 Discussion

The mechanism of an increased risk of atherosclerosis in patients with psoriasis is still not completely understood. Endothelial dysfunction has been shown to play a significant role in the pathogenesis of atherosclerosis and cardiovascular diseases [1,3,5,10]. CEPCs, a recently identified population of bone-marrow-derived cells, play a significant role in the protection and regeneration of endothelium and in the maintenance of vascular homeostasis [6,7,8,9]. A reduced number of these cells is associated with endothelial dysfunction, increased cardiovascular risk and has recently been postulated as an independent cardiovascular risk factor [7,8,9]. An impaired number of these cells was demonstrated in patients with cardiovascular diseases, cardiovascular risk factors and various IMIDs, such as rheumatoid arthritis or systemic sclerosis. Defective vasculogenesis has been postulated to have significant relevance for increased cardiovascular morbidity and mortality in various IMIDs [11,12,13,14]. To the best of our knowledge, there is only one publication regarding the evaluation of the levels of CEPCs in patients with psoriasis. Ablin et al. [15] did not show a statistically significant difference in CEPCs numbers between patients with psoriasis (n = 9), psoriatic arthritis (n = 22) and controls (n = 16). In their study CEPCs were identified as CD133+/CD34+ and CD34+/KDR+ cells in peripheral blood with flow cytometry. It should be pointed out that the number of CD34+/KDR+ cells was lower in patients with psoriatic arthritis and psoriasis compared to controls, but not significantly. The different characteristics of the study group, the limited number of patients as well as different approaches to cell quantification, especially different combinations of markers used for identification of CEPCs, may explain discrepancies in the results.

There is considerable debate on the precise phenotypic and functional definition of CEPCs that likely constitute the heterogeneous population of cells. Currently CEPCs are often enumerated with flow cytometry using different markers or their combinations that create obstacles in direct comparison to the study results [8,16]. The most widely used definition is coexpression of progenitor markers (CD133, CD34) and endothelial marker, vascular endothelial growth factor receptor-2 (VEGFR-2), also known as kinase insert domain-containing receptor (KDR), which is critical for migration, homing and differentiation of CEPCs. Expression of CD133 is lost during differentiation of endothelial progenitor cells, while mature endothelial cells express CD34, VE-cadherin, and von Willebrand factor. Therefore, different combinations of these markers seem to characterize subpopulations of CEPCs at a different maturation level [8,16]. In the current study we decided to identify CEPCs as cells double positive for CD133 and VEGFR-2 (KDR). The combination of surface markers, used in our study, seems to include both CD133+/CD34–/KDR+ and CD133+/CD34+/KDR+ progenitors and identify CEPCs subpopulation with the capacity of endothelial regeneration and new blood vessel formation. CD133+/KDR+ progenitor cells have been demonstrated to differentiate in endothelial cells both in vitro and in vivo, contribute to reendothelialization of left ventricular assist devices and promote endothelial regeneration in sites of ischemia and vascular injury in humans [17,18]. Contrary to our method, Ablin et al. [15] used another combination of surface markers that likely identifies a different subpopulation of CEPCs.

It may be suggested that reduced levels of CEPCs, demonstrated in our study, contribute to the endothelial dysfunction and increased cardiovascular risk in patients with psoriasis. The presence of classical cardiovascular risk factors may affect the number of CEPCs. However, there is growing evidence that the immune-mediated inflammatory process in psoriasis may have systemic consequences and contribute to the pathogenesis of atherosclerosis and metabolic disturbances. Recently the concept of the ‘psoriatic march’ has been presented, in which the role of systemic inflammatory process and insulin resistance, as a cause of endothelial dysfunction and subsequently atherosclerosis, is emphasized [1,3,10]. Intensity of the systemic inflammatory process in psoriasis is possibly dependent on the severity of skin manifestation, as the correlations between the PASI score and the levels of C-reactive protein, circulating proinflammatory cytokines (e.g. TNF-α) or endothelial dysfunction have been found [1,3,10,19,20]. Thus, it may be presumed that the inverse correlation between disease severity and the number of CEPCs, demonstrated in our study, indicates the impact of disease-specific factors and systemic inflammation on the number of these cells. C-reactive protein was demonstrated to directly inhibit endothelial progenitor cell differentiation, survival and function in vitro [21]. In patients with rheumatoid arthritis the number of CEPCs was lower in individuals with high levels of TNF-α compared to those with normal levels. Moreover, treatment with TNF-α inhibitor, infliximab increased the number and function of CEPCs which may contribute to its beneficial effect on endothelial function and cardiovascular risk [22,23,24,25]. Further studies are required to establish the impact of TNF-α inhibitors or other biologics on CEPCs endothelial function and cardiovascular risk in patients with psoriasis; the amelioration of inflammatory cardiovascular risk factors by these drugs may, however, suggest that they have a beneficial effect.

Expansion of dermal superficial vascular plexus appears to be an important, early event in the pathogenesis of psoriasis [26]. It may be suggested that CEPCs contribute to the expansion of superficial vascular plexus in psoriasis plaques; however, further studies are required to confirm this hypothesis. It should be pointed out that Silverman et al. [27] demonstrated that these cells are involved in the new blood vessel formation in inflamed joints in a mouse model with rheumatoid arthritis, another IMID. The contribution of CEPCs in the process of new blood vessel formation in psoriatic plaques could also explain their reduced number in our study.

VEGF is potent proangiogenic mediator that influences migration, homing, proliferation and differentiation of CEPCs and stimulates the process of angiogenesis and vasculogenesis [6,26]. The association between an increased number of CEPCs and the level of VEGF was reported [28]. We found significantly increased serum levels of VEGF in psoriatic patients compared to controls, although we failed to show any correlation between the numbers of CEPCs and levels of this factor.

sVEGFR-1 seems to play a role in the negative modulation of pathological neovascularization, possibly by sequestering the high amount of VEGF [29]. Flisiak et al. [30] reported the significantly increased levels of sVEGFR-1 and their positive correlations with disease severity, assessed with PASI, in psoriatic patients. However, we did not find any differences in the levels of sVEGFR-1 between patients and controls. Neither did we find any correlation between the levels of sVEGFR-1 and the levels of CEPCs or VEGF (data not shown).

It may be hypothesized that the reduced number of CEPCs contributes to increased cardiovascular risk in patients with psoriasis and constitutes a mechanistic link between the inflammatory process and endothelial dysfunction. However, further studies are required to confirm these speculations. It would be of interest to assess the number of these cells in patients with skin diseases that are not associated with increased cardiovascular risk, e.g. atopic dermatitis. CEPCs may represent a potential therapeutic approach to reduce the increased cardiovascular risk in psoriatic patients.


References

  1. Davidovici BB, Sattar N, Prinz JC, Puig L, Emery P, Barker JN, et al: Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol 2010;130:1785–1796.
  2. Prodanovich S, Kirsner RS, Kravetz JD, Ma F, Martinez L, Federman DG: Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol 2009;145:700–703.

    External Resources

  3. Boehncke WH, Boehncke S, Tobin AM, Kirby B: The ‘psoriatic march’: a concept of how severe psoriasis may drive cardiovascular comorbidity. Exp Dermatol 2011;20:303–307.

    External Resources

  4. Hansson GK, Hermansson A: The immune system in atherosclerosis. Nat Immunol 2011;12:204–212.
  5. Endemann DH, Schiffrin EL: Endothelial dysfunction. J Am Soc Nephrol 2004;15:1983–1992.
  6. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, et al: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.
  7. Siddique A, Shantsila E, Lip GY, Varma C: Endothelial progenitor cells: what use for the cardiologist? J Angiogenes Res 2010;22:2–6.
  8. Sen S, McDonald SP, Coates PT, Bonder CS: Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease. Clin Sci (Lond) 2011;120:263–283.
  9. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A: Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005;353:999–1007.
  10. Yiu KH, Yeung CK, Chan HT, Wong RM, Tam S, Lam KF, et al: Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation. Br J Dermatol 2011;164:514–520.

    External Resources

  11. Distler JH, Beyer C, Schett G, Lüscher TF, Gay S, Distler O: Endothelial progenitor cells: novel players in the pathogenesis of rheumatic diseases. Arthritis Rheum 2009;60:3168–3179.
  12. Pákozdi A, Besenyei T, Paragh G, Koch AE, Szekanecz Z: Endothelial progenitor cells in arthritis-associated vasculogenesis and atherosclerosis. Joint Bone Spine 2009;76:581–583.

    External Resources

  13. Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N: Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 2005;112:3337–3347.
  14. Mok MY, Yiu KH, Wong CY, Qiuwaxi J, Lai WH, Wong WS, et al: Low circulating level of CD133+KDR+cells in patients with systemic sclerosis. Clin Exp Rheumatol 2010;28:19–25.
  15. Ablin JN, Goldstein Z, Aloush V, Matz H, Elkayam O, Caspi D, et al: Normal levels and function of endothelial progenitor cells in patients with psoriatic arthritis. Rheumatol Int 2009;29:257–262.

    External Resources

  16. Timmermans F, Plum J, Yöder MC, Ingram DA, Vandekerckhove B, Case J: Endothelial progenitor cells: identity defined? J Cell Mol Med 2009;13:87–102.
  17. Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, et al: Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000;95:952–958.
  18. Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N: CD34–/CD133+/ VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res 2006;98:20–25.
  19. Borská L, Fiala Z, Krejsek J, Andrýs C, Vokurková D, Hamáková K, et al: Selected immunological changes in patients with Goeckerman’s therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8. Physiol Res 2006;55:699–706.
  20. Mussi A, Bonifati C, Carducci M, D’Agosto G, Pimpinelli F, D’Urso D, et al: Serum TNF-alpha levels correlate with disease severity and are reduced by effective therapy in plaque-type psoriasis. J Biol Regul Homeost Agents 1997;11:115–118.
  21. Verma S, Kuliszewski MA, Li SH, Szmitko PE, Zucco L, Wang CH, et al: C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation 2004;109:2058–2067.
  22. Grisar J, Aletaha D, Steiner CW, Kapral T, Steiner S, Seidinger D, et al: Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 2005;111:204–211.

    External Resources

  23. Ablin JN, Boguslavski V, Aloush V, Elkayam O, Paran D, Caspi D, George J: Effect of anti-TNF-alpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis. Life Sci 2006;79:2364–2369.
  24. Mazzoccoli G, Notarsanto I, de Pinto GD, Dagostino MP, De Cata A, D’Alessandro G, et al: Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psoriatic and rheumatoid arthritis patients. Intern Emerg Med 2010;5:495–500.

    External Resources

  25. Kerekes G, Soltész P, Dér H, Veres K, Szabó Z, Végvári A, et al: Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann NY Acad Sci 2009;1173:814–821.

    External Resources

  26. Heidenreich R, Röcken M, Ghoreschi K: Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol 2009;90:232–248.
  27. Silverman MD, Haas CS, Rad AM, Arbab AS, Koch AE: The role of vascular cell adhesion molecule 1/very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium. Arthritis Rheum 2007;56:1817–1826.
  28. Nowak K, Rafat N, Belle S, Weiss C, Hanusch C, Hohenberger P: Circulating endothelial progenitor cells are increased in human lung cancer and correlate with stage of disease. J Cardiothorac Surg 2010;37:758–763.

    External Resources

  29. Barleon B, Reusch P, Totzke F, Herzog C, Keck C, Martiny-Baron G, et al: Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors. Angiogenesis 2001;4:143–154.
  30. Flisiak I, Zaniewski P, Rogalska M, Myśliwiec H, Jaroszewicz J, Chodynicka B: Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales. Cytokine 2010;52:225–229.

  

Author Contacts

Aleksandra Batycka-Baran, MD, PhD
Department of Dermatology, Venereology and Allergology
Wroclaw Medical University, ul. Chalubinskiego 1
PL–50368 Wroclaw (Poland)
Tel. +48 71 3270 941, E-Mail ola.batycka@interia.pl

  

Article Information

Received: May 2, 2012
Accepted after revision: June 20, 2012
Published online: September 11, 2012
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 3, Number of References : 30

  

Publication Details

Dermatology

Vol. 225, No. 1, Year 2012 (Cover Date: October 2012)

Journal Editor: Saurat J.-H. (Geneva)
ISSN: 1018-8665 (Print), eISSN: 1421-9832 (Online)

For additional information: http://www.karger.com/DRM


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Psoriasis is associated with an increased cardiovascular risk. Circulating endothelial progenitor cells (CEPCs) play a significant role in the maintenance of vascular homeostasis. Objective: The aim of this study was to evaluate the number of CEPCs in patients with psoriasis compared to controls and assess possible correlations between the number of these cells and the plasma levels of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and clinical features of psoriasis. Methods: The number of CEPCs, identified as CD133+/KDR+ cells, was determined with flow cytometry in peripheral blood of psoriatic patients (n = 63) and controls (n = 31). The plasma levels of VEGF and sVEGFR-1 were measured with enzyme-linked immunosorbent assay. Results: The number of CEPCs was significantly reduced in psoriatic patients compared with controls (p = 0.000026) and inversely correlated with disease severity (R = –0.283; p = 0.0248). Conclusion: A reduced number of CEPCs may contribute to endothelial dysfunction in patients with psoriasis.

© 2012 S. Karger AG, Basel


  

Author Contacts

Aleksandra Batycka-Baran, MD, PhD
Department of Dermatology, Venereology and Allergology
Wroclaw Medical University, ul. Chalubinskiego 1
PL–50368 Wroclaw (Poland)
Tel. +48 71 3270 941, E-Mail ola.batycka@interia.pl

  

Article Information

Received: May 2, 2012
Accepted after revision: June 20, 2012
Published online: September 11, 2012
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 3, Number of References : 30

  

Publication Details

Dermatology

Vol. 225, No. 1, Year 2012 (Cover Date: October 2012)

Journal Editor: Saurat J.-H. (Geneva)
ISSN: 1018-8665 (Print), eISSN: 1421-9832 (Online)

For additional information: http://www.karger.com/DRM


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 5/2/2012 8:19:02 AM
Accepted: 6/20/2012
Published online: 9/11/2012
Issue release date: October 2012

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 3

ISSN: 1018-8665 (Print)
eISSN: 1421-9832 (Online)

For additional information: http://www.karger.com/DRM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Davidovici BB, Sattar N, Prinz JC, Puig L, Emery P, Barker JN, et al: Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol 2010;130:1785–1796.
  2. Prodanovich S, Kirsner RS, Kravetz JD, Ma F, Martinez L, Federman DG: Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol 2009;145:700–703.

    External Resources

  3. Boehncke WH, Boehncke S, Tobin AM, Kirby B: The ‘psoriatic march’: a concept of how severe psoriasis may drive cardiovascular comorbidity. Exp Dermatol 2011;20:303–307.

    External Resources

  4. Hansson GK, Hermansson A: The immune system in atherosclerosis. Nat Immunol 2011;12:204–212.
  5. Endemann DH, Schiffrin EL: Endothelial dysfunction. J Am Soc Nephrol 2004;15:1983–1992.
  6. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, et al: Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85:221–228.
  7. Siddique A, Shantsila E, Lip GY, Varma C: Endothelial progenitor cells: what use for the cardiologist? J Angiogenes Res 2010;22:2–6.
  8. Sen S, McDonald SP, Coates PT, Bonder CS: Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease. Clin Sci (Lond) 2011;120:263–283.
  9. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A: Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005;353:999–1007.
  10. Yiu KH, Yeung CK, Chan HT, Wong RM, Tam S, Lam KF, et al: Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation. Br J Dermatol 2011;164:514–520.

    External Resources

  11. Distler JH, Beyer C, Schett G, Lüscher TF, Gay S, Distler O: Endothelial progenitor cells: novel players in the pathogenesis of rheumatic diseases. Arthritis Rheum 2009;60:3168–3179.
  12. Pákozdi A, Besenyei T, Paragh G, Koch AE, Szekanecz Z: Endothelial progenitor cells in arthritis-associated vasculogenesis and atherosclerosis. Joint Bone Spine 2009;76:581–583.

    External Resources

  13. Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N: Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 2005;112:3337–3347.
  14. Mok MY, Yiu KH, Wong CY, Qiuwaxi J, Lai WH, Wong WS, et al: Low circulating level of CD133+KDR+cells in patients with systemic sclerosis. Clin Exp Rheumatol 2010;28:19–25.
  15. Ablin JN, Goldstein Z, Aloush V, Matz H, Elkayam O, Caspi D, et al: Normal levels and function of endothelial progenitor cells in patients with psoriatic arthritis. Rheumatol Int 2009;29:257–262.

    External Resources

  16. Timmermans F, Plum J, Yöder MC, Ingram DA, Vandekerckhove B, Case J: Endothelial progenitor cells: identity defined? J Cell Mol Med 2009;13:87–102.
  17. Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, et al: Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000;95:952–958.
  18. Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N: CD34–/CD133+/ VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res 2006;98:20–25.
  19. Borská L, Fiala Z, Krejsek J, Andrýs C, Vokurková D, Hamáková K, et al: Selected immunological changes in patients with Goeckerman’s therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8. Physiol Res 2006;55:699–706.
  20. Mussi A, Bonifati C, Carducci M, D’Agosto G, Pimpinelli F, D’Urso D, et al: Serum TNF-alpha levels correlate with disease severity and are reduced by effective therapy in plaque-type psoriasis. J Biol Regul Homeost Agents 1997;11:115–118.
  21. Verma S, Kuliszewski MA, Li SH, Szmitko PE, Zucco L, Wang CH, et al: C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function: further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation 2004;109:2058–2067.
  22. Grisar J, Aletaha D, Steiner CW, Kapral T, Steiner S, Seidinger D, et al: Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 2005;111:204–211.

    External Resources

  23. Ablin JN, Boguslavski V, Aloush V, Elkayam O, Paran D, Caspi D, George J: Effect of anti-TNF-alpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis. Life Sci 2006;79:2364–2369.
  24. Mazzoccoli G, Notarsanto I, de Pinto GD, Dagostino MP, De Cata A, D’Alessandro G, et al: Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psoriatic and rheumatoid arthritis patients. Intern Emerg Med 2010;5:495–500.

    External Resources

  25. Kerekes G, Soltész P, Dér H, Veres K, Szabó Z, Végvári A, et al: Effects of biologics on vascular function and atherosclerosis associated with rheumatoid arthritis. Ann NY Acad Sci 2009;1173:814–821.

    External Resources

  26. Heidenreich R, Röcken M, Ghoreschi K: Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol 2009;90:232–248.
  27. Silverman MD, Haas CS, Rad AM, Arbab AS, Koch AE: The role of vascular cell adhesion molecule 1/very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium. Arthritis Rheum 2007;56:1817–1826.
  28. Nowak K, Rafat N, Belle S, Weiss C, Hanusch C, Hohenberger P: Circulating endothelial progenitor cells are increased in human lung cancer and correlate with stage of disease. J Cardiothorac Surg 2010;37:758–763.

    External Resources

  29. Barleon B, Reusch P, Totzke F, Herzog C, Keck C, Martiny-Baron G, et al: Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors. Angiogenesis 2001;4:143–154.
  30. Flisiak I, Zaniewski P, Rogalska M, Myśliwiec H, Jaroszewicz J, Chodynicka B: Effect of psoriasis activity on VEGF and its soluble receptors concentrations in serum and plaque scales. Cytokine 2010;52:225–229.